Using DNA damage to target osteosarcoma

The challenge

Osteosarcoma is the most common type of bone cancer in children and young people. Treatments can involve major surgery and intensive chemotherapy, but they do not work for every patient. Researchers are looking for new weaknesses in osteosarcoma cells that could lead to more targeted treatments.

Osteosarcoma cells have especially fragile DNA. This characteristic is called ‘genomic instability’ and means that the cancer’s DNA is constantly accumulating damage and genetic mistakes. This isn’t unique to osteosarcoma. Other cancers also have high levels of DNA damage and mistakes. Professor Sophie Postel-Vinay’s team at University College London recently found that breast cancer cells with genomic instability can only survive when a molecule, called M1, is present. M1 helps cancer cells to cope with damaged DNA and also enables them to hide from the immune system. In breast cancer, the researchers found that blocking M1 led to cancer cell death due to DNA damage and an uncontrolled response from the immune system.
 

The project

In this project, Prof Postel-Vinay’s team want to find out whether osteosarcoma cells have the same weakness as breast cancers. They hope that blocking M1 will trigger cell death in a range of osteosarcoma cell samples from patients. The team want to find out:

• Do cancer cells die when M1 is removed, and does this depend on how much DNA damage the cancer cell has?
• Do the cells that die have specific genetic errors or changes? This could help doctors identify which patients are most likely to benefit from treatments targeting M1.
• Do cancer cells die due to DNA damage, an immune response, or a combination of both?
   

The impact

If the osteosarcoma cells do rely on M1 for their survival, this could lead to the development of a clinical trial that can evaluate drugs targeting M1 as a new osteosarcoma treatment. The researchers have previously developed clinical trials based on their lab work, so are well placed to take this research forwards. By identifying a new weakness in osteosarcoma cells, Prof Postel-Vinay and Dr Cottone hope this work could pave the way for new treatments for children and young people with osteosarcoma.